2,2-dimethylpropane-1,3-diyl dibenzoate

Endpoint summary

Description of key information

There are acute toxicity studies available using different application routes. Thus, the conditions according to Regulation (EC) 1907/2006 (REACH) ANNEX VIII, section 8.5 column 2 are fulfilled. The results of these studies show that 2,2-dimethylpropane-1,3-diyl dibenzoate is practically non-toxic.
LD50 (oral, dermal) > 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to the Guideline of today, but without gross pathology and without GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- yellowish white chunks

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-244 g
- Fasting period before study: diet was withheld for up to 18 hours before doseing
- Housing: in groups of 5
- Diet ad libitum
- Water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- temperature and humidity controlled quarters
- The animals were maintained in accordance with the recommendations contained in H.E.W. Publication No.74-23 (N.I.H.) entitled "Guide for the care and use of laboratory animals"

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test material was administered orally by gavage as a suspension in corn oil. The dosage was administered at a volume of 20 ml/kg.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

5 males and 5 females were used in this study. The test material was administered orally by gavage as a suspension in corn oil. The dosage level was administered at a volume of 20 mg/kg. Observations for toxic signs were recorded during the first 4 hours following dosing, at 24 hours and daily thereafter for a total of 14 days. The rats were observed for mortality, clinical signs and body weight development.

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: No rat died. All rats showed weight gain. Some rats developed hypoactivity, urine stained abdomen and diarrhea, but returned to normal within the 14 day observation period.

Mortality:

No rat died.

Clinical signs:

other: Some rats developed hypoactivity, urine stained abdomen and diarrhea, but returned to normal within the 14 day observation period.

Gross pathology:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

Five male and 5 female Sprague-Dawley rats received a single dose of 5000 mg/kg bw. The rats were observed for mortality, clinical signs and body weight development. No rat died. The discriminating dose is 5000 mg/kg bw.

Executive summary:

5 male and 5 female Sprague-Dawley rats were used to examine the acute oral toxicity in a study similar to the Guideline of today. There is no information on GLP and or gross pathology. 5000mg/kg bw of the test material was administered orally by gavage as a suspension in corn oil. The dosage level was administered at a volume of 20 ml/kg. Observations for pharmacotoxic signs were recorded during the first 4 hours following dosing, at 24 hours and daily thereafter for a total of 14 days. The rats were observed for mortality, clinical signs and body weight development. No rat died. All rats showed weight gain. Some rats developed hypoactivity, urine stained abdomen and diarrhea, but returned to normal within the 14 day observation period. Thus, the LD50 is > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

In addition to the study reported by Wilson (1978) there is an earlier study performed in 1972. Both studies lead to the conclusion that 2,2-dimethylpropane-1,3-diyl dibenzoate is practically non-toxic.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

In addition to the acute oral study there is another valid acute study available using dermal exposure route resulting in LD50 values, which can be taken into account. Thus, there is no need to perform an acute inhalation toxicity study and to determine a LC50 value, because the conditions according to Regulation (EC) 1907/2006 (REACH), ANNEX VIII, section 8.5, column 2 are fulfilled.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Despite the low number of animals and the lack of gross pathological examination the evaluable report provided sufficient information to evaluate this endpoint.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Low number of animals in test and no necropsy is performed at the end of the observation time.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- yellowish white chunks

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2310-2381 g
- Housing: individually
- Diet ad libitum
- Water ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- temperature and humidity controlled quarters
- The animals were maintained in accordance with the recommendations contained in H.E.W. Publication No.74-23 (N.I.H.) entitled "Guide for the care and use of laboratory animals"

Type of coverage:

semiocclusive

Vehicle:

physiological saline

Details on dermal exposure:

The test material was applied once only to the shaved backs of the rabbits at a dosage level of 20000 mg/kg bw for 24 hours. Physiological saline was used as a wetting agent.

Duration of exposure:

24 hours

Doses:

20000 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

other: untreated area at the opposite site

Details on study design:

2 male and 2 female rabbits were used. The hair was removed from the back of the rabbits (20-30 % of the body surface) with an electric clipper. The skin of 2 rabbits was abraded. The test material was applied once only to the shaved backs of the rabbits at a dosage level of 20000 mg/kg bw for 24 hours. Physiological saline was used as a wetting agent. The opposite site of the treatment area served as control. The treated area were covered by semiocclusive dressing. After 24 hours of exposure the bandages were removed and animals were observed for mortality, clinical signs , body weight development and local effects at the treatment area up to 14 days post exposure.

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Remarks on result:

other: No rabbit died. All rabbits appeared normal and gained body weight. Some animals showed slight to very slight discoloration at the treated area, but recovered within the 14 day observation period.

Mortality:

No rabbit died.

Clinical signs:

other: All rabbits appeared normal.

Gross pathology:

Gross pathological examination was not performed.

Interpretation of results:

GHS criteria not met

Conclusions:

2,2-dimethylpropane-1,3-diyl dibenzoate was applied once only to the shaved backs of the rabbits at a dosage level of 20000 mg/kg bw for 24 hours. No rabbit died. All rabbits appeared normal and gained body weight. Thus, the LD50 is > 20000 mg/kg bw.

Executive summary:

Despite the low number of animals and the lack of gross pathological examination the following examination is similar to the guideline of today and is valid for evaluation of this endpoint: To examine the acute dermal toxicity 2 male and 2 female rabbits were used. The hair was removed from the back of the rabbits (20-30 % of the body surface) with an electric clipper. The skin of 2 rabbits was abraded. The test material was applied once only to the shaved backs of the rabbits at a dosage level of 20000 mg/kg bw for 24 hours. Physiological saline was used as a wetting agent. The opposite site of the treatment area served as control. The treated area were covered by semiocclusive dressing. After 24 hours of exposure the bandages were removed and animals were observed for mortality, clinical signs, body weight development and local effects at the treatment area up to 14 days post exposure. No rabbit died. All rabbits appeared normal and gained body weight. Some animals showed slight to very slight discoloration at the treated area, but recovered within the 14 day observation period. Thus, the LD50 is > 20000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

20 000 mg/kg bw

Quality of whole database:

There is only one study available. This study is performed similar to the requirements of the guideline of today. Therefore, it is evaluated with Klimisch score 2.

Additional information

Acute oral toxicity

5 male and 5 female Sprague-Dawley rats were used to examine the acute oral toxicity in a study similar to the guideline of today. There is no information on GLP and or gross pathology. 5000 mg/kg bw of the test material was administered orally by gavage as a suspension in corn oil. The dosage level was administered at a volume of 20 ml/kg. Observations for toxic signs were recorded during the first 4 hours following dosing, at 24 hours and daily thereafter for a total of 14 days. The rats were observed for mortality, clinical signs and body weight development. No rat died; all rats showed weight gain. Some rats developed hypoactivity, urine stained abdomen and diarrhea but returned to normal within the 14 day observation period. Thus, the LD50 is > 5000 mg/kg bw (Wilson, 1978). The result of this study confirms the result of an earlier study yielding a LD50 value for male and female rats of 6011 mg/kg bw.

Overall, despite of some unspecific reactions following administration the test material is to be evaluated as practically non-toxic.

 

Acute dermal toxicity

Despite the low number of animals and the lack of gross pathological examination the following examination is similar to the guideline of today and is valid for evaluation of this endpoint: To examine the acute dermal toxicity 2 male and 2 female rabbits were used. The hair was removed from the back of the rabbits (20-30 % of the body surface) with an electric clipper. The skin of 2 rabbits was abraded. The test material was applied once only to the shaved backs of the rabbits at a dosage level of 20000 mg/kg bw for 24 hours. Physiological saline was used as a wetting agent. The opposite site of the treatment area served as control. The treated areas were covered by semiocclusive dressing. After 24 hours of exposure the bandages were removed and animals were observed for mortality, clinical signs, body weight development and local effects at the treatment area up to 14 days post exposure. No rabbit died. All rabbits appeared normal and gained body weight. Some animals showed slight to very slight discoloration at the treated area, but recovered within the 14 day observation period. Thus, the LD50 is > 20000 mg/kg bw.

 

Acute toxicity by inhalation

In addition to the acute oral study there is another valid acute study available using dermal exposure route resulting in a LD50 value which can be taken into account. Thus, there is no need to perform an acute inhalation toxicity study and to determine a LC50 value, because the conditions according to Regulation (EC) 1907/2006 (REACH) ANNEX VIII, section 8.5 column 2 are fulfilled.

 

For completeness purposes it should be mentioned that there is a study on rats being exposed to essential saturated vapor for 6 hours. During the following 14 day observation time the rats were observed for clinical signs, mortality, body weight development and finally for gross pathological changes after necropsy.

The immediate response of the rats to the experimental atmosphere was an increase in activity in preening. After several minutes of exposure, this activity decreased. No pathological signs were observed. No death occurred during exposure and during post exposure observation time of 14 days. Except of 2/5 females all 10 rats have gained weight after 14 days, and gross pathology revealed no adverse effects. The calculated concentration of the vapor in the chamber atmosphere was about 0.16 mg/l (approx. 160 mg/m³).

 

Overall conclusion

There are acute toxicity studies available using different application routes. Thus, the conditions according to Regulation (EC) 1907/2006 (REACH) ANNEX VIII, section 8.5 column 2 are fulfilled.

Justification for selection of acute toxicity – oral endpoint
The acute oral study which was taken into account is performed similar to the requirements of the guideline of today. Therefore, it is evaluated with Klimisch score 2.

Justification for selection of acute toxicity – inhalation endpoint
In addition to the acute oral study there is another valid acute study available using dermal exposure route resulting in LD50 values, which can be taken into account. Thus, there is no need to perform an acute inhalation toxicity study and to determine a LC50 value, because the conditions according to Regulation (EC) 1907/2006 (REACH), ANNEX VIII, section 8.5, column 2 are fulfilled.

Justification for selection of acute toxicity – dermal endpoint
There is only one study available. This study is performed similar to the requirements of the guideline of today. Therefore, it is evaluated with Klimisch score 2.

Justification for classification or non-classification

In the key study for acute oral toxicity the discriminating dose was 5000 mg/kg bw and in the key study for acute dermal toxicity the discriminating dose was 20000 mg/kg bw.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.